Cracking the Code of Life

NOVA chronicles the race to reach one of the greatest milestones in the history of science: decoding the human genome.
Airing April 17, 2001 at 9 pm on PBS
Aired April 17, 2001 on PBS

Program Description

This two-hour special, hosted by ABC "Nightline" correspondent Robert Krulwich, chronicles the fiercely competitive race to capture one of the biggest scientific prizes ever: the complete letter-by-letter sequence of genetic information that defines human life—the human genome. NOVA tells the story of the genome triumph and its profound implications for medicine and human health.

Transcript

Cracking the Code of Life

ROBERT KRULWICH: When I look at this—and these are the
three billion chemical letters, instructions for a human being—my eyes glaze
over. But when scientist Eric Lander looks at this he sees stories.

ERIC LANDER (Whitehead Institute/MIT): The genome is a storybook
that's been edited for a couple billion years. And you could take it to bed
like A Thousand and One Arabian Nights, and read a different story in
the genome every night.

ROBERT KRULWICH: This is the story of one of the greatest
scientific adventures ever, and at the heart of it is a small, very powerful
molecule, DNA.

For the past ten years, scientists all over the world have been
painstakingly trying to read the tiny instructions buried inside our DNA. And
now, finally, the "Human Genome" has been decoded.

J. CRAIG VENTER (President, Celera Genomics): We're at the moment
that scientists wait for. This is what we wanted to do, you know? We're now
examining and interpreting the genetic code.

FRANCIS COLLINS (National Human Genome Research Institute): This
is the ultimate imaginable thing that one could do scientifically...is to go
and look at our own instruction book and then try to figure out what it's
telling us.

ROBERT KRULWICH: And what it's telling us is so surprising and
so strange and so unexpected. Fifty percent of the genes in a banana are in
us?

ERIC LANDER: How different are you from a banana?

ROBERT KRULWICH: I feel...and I feel I can say this with some
authority...very different from a banana.

ERIC LANDER: You may feel different...

ROBERT KRULWICH: I eat a banana.

ERIC LANDER: All the machinery for replicating your DNA, all the
machinery for controlling the cell cycle, the cell surface, for making
nutrients, all that's the same."

ROBERT KRULWICH: So what does any of this information have to
do with you or me? Perhaps more than we could possibly imagine. Which one of us
will get cancer or arthritis or Alzheimer's? Will there be cures? Will parents
in the future be able to determine their children's genetic
destinies?

ERIC LANDER: We've opened a box here that has got a huge amount of
valuable information. It is the key to understanding disease and in the long
run to curing disease. But having opened it, we're also going to be very
uncomfortable with that information for some time to come.

ROBERT KRULWICH: Yes, some of the information you are about to
see will make you very uncomfortable. On the other hand, some of it I think
you'll find amazing and hopeful.

I'm Robert Krulwich. And tonight we will not only report the latest
discoveries of the Human Genome project, you will meet the people who made
those discoveries possible, and who competed furiously to be first to be
done.

And as you watch our program on the human genome, we will be raising a
number of issues: genes and privacy, genes and corporate profits, genes and the
odd similarity between you and the yeast. And we'd like to have your thoughts
on all these subjects. So please, if you will, log on to NOVA's Website—it's
located at pbs.org...it'll be there after the broadcast, so do it after the
broadcast—where you can take a survey. The results will be immediately
available and continually updated. We'll be right back.

Major funding for NOVA is provided by the Park Foundation, dedicated to
education and quality television.

This program is funded in part by the Northwestern Mutual Foundation. Some
people already know Northwestern Mutual can help plan for your children's
education. Are you there yet? Northwestern Mutual Financial Network.

Scientific achievement is fueled by the simple desire to make things clear.
Sprint PCS is proud to support NOVA.

Major funding for this program is provided by the National Science
Foundation, America's investment in the future. And by the Corporation for
Public Broadcasting, and by contributions to your PBS station from viewers like
you. Thank You.

ROBERT KRULWICH: To begin, let's go back four and some billion
years ago to wherever it was that the first speck of life appeared on earth,
maybe on the warm surface of a bubble. That speck did something that has gone
on uninterrupted ever since. It wrote a message. It was a chemical message
that it passed to its children, which then passed it on to its children, and to
its children, and so on. The message has passed from the very first organism,
all the way down through time, to you and me—like a continuous thread through
all living things.

It's more elaborate now, of course, but that message, very simply, is the
secret of life. And here is that message contained in this stunning little
constellation of chemicals we call DNA. You've seen it in this form, the
classic double helix, but since we're going to be spending a lot of time
talking about DNA, I wondered, "What does it look like when it's raw, you know,
in real life?" So I asked an expert.

ERIC LANDER: DNA has a reputation for being such a mystical
high-falutin' sort of molecule—all this information, your future, your
heredity. It's actually goop. So this here's DNA.

ROBERT KRULWICH: Professor Eric Lander is a geneticist at
MIT's Whitehead Institute.

ERIC LANDER: It's very, very long strands of molecules, these double
helices of DNA, which, when you get them all together, just look like little
threads of cotton.

ROBERT KRULWICH: And these strands were literally pulled from
cells, blood cells or maybe skin cells of a human being?

ERIC LANDER: Whoever contributed this DNA, you can tell from this
whether or not they might be at early risk for Alzheimer's disease, you can
tell whether or not they might be at early risk for breast cancer. And there's
probably about 2000 other things you can tell that we don't know how to tell
yet but will be able to tell. And it's really incredibly unlikely that you can
tell all that from this. But that's DNA for you. That apparently is the secret
of life just hanging off there on the tube.

ROBERT KRULWICH: And already DNA has told us things that no
one...no one had expected. It turns out that human beings have only twice as
many genes as a fruit fly. Now how can that be? We are such complex and
magnificent creatures and fruit flies...well they're fruit flies. DNA also
tells us that we are more closely related to worms and to yeast than most of us
would ever have imagined.

But how do you read what's inside a molecule? Well, if it's DNA, if you
turn it so you can look at it from just the right angle, you will see in the
middle what look like steps in a ladder. Each step is made up of two chemicals,
cytosine and guanine or thymine and adenine. They come always in pairs, called
base pairs, either C and G, or T and A for short. This is, step by step, a
code, three billion steps long—the formula for a human being.

ROBERT KRULWICH: We're all familiar with this thing, this
shape is very familiar.

ERIC LANDER: ...double helix...

ROBERT KRULWICH: ...double helix. First of all, I'm
wondering...this is my version of a DNA molecule. Is this, by the way, what it
looks like?

ERIC LANDER: Well, give or take. I mean, a cartoon version, yeah.

ROBERT KRULWICH: Cartoon version?

ERIC LANDER: A little like that or so, yeah.

ROBERT KRULWICH: So there are...in every...almost every cell
in your body, if you look deep enough, you will find this chain
here?

ERIC LANDER: Oh yes, stuck in the nucleus of your cell.

ROBERT KRULWICH: Now how small is this, if in a real DNA
molecule the distance between the two walls is how wide?

ERIC LANDER: Oh golly...

ROBERT KRULWICH: Look at this. He's asking for
help.

ERIC LANDER: This distance is about from...this distance is about 10
angstroms.

ROBERT KRULWICH: That's one billionth of a meter when it's
clumped up in a very particular way.

ERIC LANDER: Well no, it's curled up some like that but you see it's
more than that. You can't curl it up too much because these little negatively
charged things will repel each other so you fold it on its...I'm going to break
your molecule.

ROBERT KRULWICH: No, don't break my molecule...very
valuable.

ERIC LANDER: You got this. And then it's folded up like this. And then
those are folded up on top of each other. And so, in fact, if you were to
stretch out all of the DNA it would run, oh, I don't know, thousands and
thousands of feet.

ROBERT KRULWICH: But the main thing about this is the
ladder, the steps of this ladder. If I knew it was A and T and C and C and G
and G and A...

ERIC LANDER: No, no. It's not G and G, it's G and C.

ROBERT KRULWICH: I'm sorry, whatever the rules are of the
grammar, yeah...if I could read each of the individual ladders, I might find
the picture of what?

ERIC LANDER: Well, of your children. This is what you pass to your
children. You know people have known for 2000 years that your kids look a lot
like you. Well it's because you must pass them something, some instructions
that give them the eyes they have and the hair color they have and the nose
shape they do. And the only way you pass it to them is in these sentences.
That's it.

ROBERT KRULWICH: And to show you the true power of this
molecule, we're going to start with one atom deep inside, and we pull back and
you see it form its As and Ts and Cs and Gs and the classic double spiral. And
then it starts the mysterious process that creates a healthy new baby. And the
interesting thing is that every human baby, every baby born, is 99.9 percent
identical in its genetic code to every other baby.

So the tiniest differences in our genes can be hugely important, can
contribute to differences in height, physique, maybe even talents, aptitudes
and can also explain what can break, what can make us sick.

Cracking the code of those minuscule differences in DNA that influence
health and illness is what the Human Genome Project is all about. Since 1990,
scientists all over the world in university and government labs, have been
involved in a massive effort to read all three billion As, Ts, Gs, and Cs of
human DNA.

They predicted it would take at least 15 years. That was partly because in
the early days of the project, a scientist could spend years...an entire career
trying to read just a handful of letters in the human genome. It took 10 years
to find the one genetic mistake that causes cystic fibrosis. Another 10 years
to find the gene for Huntington's disease. Fifteen years to find one of the
genes that increase the risk for breast cancer. One letter at a time, painfully
slowly...

ROBERT WATERSTON: One, two, three, four, five...

ROBERT KRULWICH: ...frustratingly prone to
mistakes...

ROBERT WATERSTON (DNA mapping pioneer): ...Cs in a row.

NARRATOR: ...and false leads.

We asked Dr. Robert Waterston, a pioneer in mapping DNA, to show us the way
it used to be done.

ROBERT WATERSTON: The original ladders for DNA sequence, we actually
read by putting a little letter next to the band that we were calling and then
writing those down on a piece of paper or into the computer after that. It's
horrendous.

ROBERT KRULWICH: And we haven't mentioned the hardest part.
This here, magnified 50,000 times is an actual clump of DNA, chromosome 17. Now
if you look inside you will find, of course, hundreds of millions of As, and
Cs, and Ts and Gs, but it turns out that only about one percent of them are
active and important. These are the genes that scientists are searching for. So
somewhere in this dense chemical forest are genes involved in deafness,
Alzheimer's, cancer, cataracts. But where? This is such a maze scientists need
a map. But at the old pace that would take close to forever.

ROBERT WATERSTON: C and then an A.

ROBERT KRULWICH: And then came the revolution. In the last ten
years the entire process has been computerized. That cost hundreds of millions
of dollars. But now, instead of decoding a few hundred letters by hand in a
day, together these machines can do a thousand every second and that has made
all the difference.

ROBERT COOK-DEEGAN (National Research Council): This is something
that's going to go in the textbooks. Everybody knows that. Everybody, when the
Genome project was being born, was consciously aware of their role in
history.

ROBERT KRULWICH: Getting the letters out is...has been
described as finding the blueprint of a human being, finding a manual for a
human being, finding the code of the human being. What's your
metaphor?

ERIC LANDER: Oh, golly gee. I mean, you can have very high falutin'
metaphors for this kind of stuff. This is basically a parts list. Blueprints
and all these fancy... It's just a parts list. It's a parts list with a lot of
parts. If you take an airplane, a Boeing 777, I think it has like 100,000
parts. If I gave you a parts list for the Boeing 777 in one sense you'd know a
lot. You'd know 100,000 components that have got to be there, screws and wires
and rudders and things like that. On the other hand, I bet you wouldn't know
how to put it together. And I bet you wouldn't know why it flies. Well we're in
the same boat. We now have a parts list. That's what the human genome project
is about is getting the parts list. If you want to understand the plane you
have to have the parts list but that's not enough to understand why it flies.
Of course you'd be crazy not to start with the parts list.

ROBERT KRULWICH: And one reason it's so important to
understand all those parts, to decode every letter of the genome, is because
sometimes, out of three billion base pairs in our DNA, just one single letter
can make a difference.

Allison and Tim Lord are parents of two-year-old Hayden.

TIM LORD (Father of son with Tay Sachs): The two things that I
think of the most about Hayden, which a lot of people got from him right from
the beginning is that he was always, I thought, very funny. I mean he loved to
smile and laugh and he just used to guffaw. And this was later when he was
about a year old, he just found the funniest things hilarious. And so he and I
would just crack each other up.

ROBERT KRULWICH: Hayden seemed to be developing normally for
the first few months but Allison began to notice that some things were not
quite right.

ALLISON LORD (Mother of son with Tay Sachs): I was very anxious
all the time with Hayden. I sensed that something was not the same. I would see
my friends changing the diaper of their child who was around the same age,
their newborn, and see the physical movement, and the legs moving, and things
like that, and Hayden didn't do that.

ROBERT KRULWICH: Doctors told them that Hayden was just
developing a bit slowly. But by the time he turned a year old, it was clear
something serious was wrong. He never crawled, he never talked, he never ate
with his fingers and he seemed to be going backwards, not
progressing.

TIM LORD: I remember the last time he laughed. And I took a trip with
him out to pick up a suit because we were going to a wedding that night, and we
came back and it was really windy, and he just loves to feel the wind, and so
we had a great time. We came back and I propped him up right here on the couch
and I was sitting next to him and he just kind of threw his head back and
laughed, like, you know, what a fun trip, you know? And that the last time he
was able to laugh. That's really hard.

ROBERT KRULWICH: It turned out that Hayden had Tay Sachs
disease, a genetic condition that slowly destroys a baby's brain.

DR. EDWIN KOLODNY (NYU, Department of Neurology): What happens is
the child appears normal at birth, and over the course of the first year begins
to miss developmental milestones. So at six months a child should be turning
over—a child is unable to turn over, to sit up, to stand, to walk, to talk.

ROBERT KRULWICH: Tay Sachs begins at one infinitesimal spot on
the DNA ladder, when just one letter goes wrong. Say this cluster of atoms is
a picture of that letter, a mistake here can come down to just four atoms.
That's it. But since genes create proteins, that error creates a problem in
this protein which is supposed to dissolve the fat in the brain. But
now the protein doesn't work. So fat builds up, swells the brain, and
eventually strangles and crushes critical brain cells. And all of this is the
result of one bad letter in that baby' s DNA.

DR. EDWIN KOLODNY: In most cases it's a single base change. As we say, a
letter difference.

ROBERT KRULWICH: One defective letter out of three billion,
and no way to fix it.

TIM LORD: That's my boy.

ROBERT KRULWICH: Tay Sachs is a relentlessly progressive
disease. In the year since his diagnosis, Hayden has gone blind. He can't eat
solid food. It's harder and harder for him to swallow. He can't move on his own
at all. And he has seizures as often as 10 times a day.

DR. EDWIN KOLODNY: For children with classical Tay Sachs Disease,
there's only one outcome. And children die by the age of five to seven,
sometimes even before age five.

ROBERT KRULWICH: As it happens, Tim Lord has an identical twin
brother. When Hayden was diagnosed, that brother, Charlie, went to New York to
be with Tim. And of course, Charlie called his wife Blyth to tell her the news.
Blyth had been Allison's roommate in college and her best friend.

BLYTH LORD (Mother of daughter with Tay Sachs): Charlie told me
that Hayden had Tay Sachs. He called me on the phone and he told me
immediately what it was. I went up into the computer and looked it up and then
just couldn't believe what I read.

ROBERT KRULWICH: Blyth and Charlie had a three-year- old
daughter, Taylor, and a baby girl named Cameron. Cameron was healthy and happy
except for one small thing.

BLYTH LORD: On the NTSAD Website it talks about typically between six
and eight months is when the signs start coming, but one of the early signs is
that they startle easily. And Hayden had always had a really heavy startle
response. But we had noticed that Cameron had a comparable startle response.
Not quite as severe but absolutely not like Taylor had had.

ROBERT KRULWICH: As soon as she saw that early warning sign on
the Tay Sachs Website, Blyth went to get herself and Cameron tested.

CHARLIE LORD (Mother of daughter with Tay Sachs): It was another
week. It was exactly a week until we got the final results on Cameron's blood
work. And then the Tuesday before Thanksgiving we went into our pediatrician's
office and he had the results, and we found out that night that Blyth was a
carrier and that Cameron had Tay Sachs.

BLYTH LORD: He said...all he said was, "I'm sorry."

ROBERT KRULWICH: Tay Sachs is a very rare condition and it
usually occurs in specific groups, like Ashkenazi Jews. And even then, the baby
must inherit the bad gene from both parents. So even though there is a Tay
Sachs test, the Lords had no reason to think they would be at risk. And yet
incredibly, all four of them, Tim and Charlie and both their wives—all four
were carriers. That was an unbelievably bad roll of the genetic
dice.

TIM LORD: Charlie and I are incredibly close and have been all our
lives. And when I think about him and Blyth having to go through this, it just
seems really cruel. It just seems too much.

CHARLIE LORD: I had already geared myself up for being my brother's rock
and I couldn't imagine having to help him and go through it myself.

ROBERT KRULWICH: For families like the Lords, and for
everybody, the Human Genome project offers the chance to find out early if
we're at risk for all kinds of diseases.

TIM LORD: I would like to see a really aggressive push to develop a test
for hundreds of genetic diseases so that parents could be informed before they
started to have children as to the dangers that face them. And I think it's
within our grasp. Now that they've mapped the human genome, I mean, the
information is there for people to begin to sort through. They're horrible,
horrible, horrible diseases and if there's any way that you can be tested for a
whole host of them and not have them affect a child, I think it's something
that we have to focus on.

ROBERT KRULWICH: Hayden Lord died a few months before his
third birthday. What makes this story especially hard to bear is we now know
that a loss that huge—and it was a catastrophe, by any measure—started with a
single error, a few atoms across, buried inside a cell.

Now, that something so small could trigger such an enormous result is a
perspective that is incredibly frightening. Except that now geneticists have
figured out how to see many of these tiny errors before they become
catastrophes. When you think about that, that's an extraordinary thing, to spot
a catastrophe when it's still an insignificant dot in a cell, which is the
promise of the Human Genome Project. It is, first and foremost, an early
warning system for a host of diseases which will give, hopefully, parents,
doctors and scientists an advantage that we have never had before. Because when
you can see trouble coming way, way before it starts you have a chance to stop
it, or treat it. Eventually you might cure it.

And that's why, when Congress created the Human Genome Project in 1990, the
challenge was to get a complete list of our As, Ts, Cs and Gs as quickly as
possible, so the business of making tests, medicines, and cures could begin.
They figured it would take about 15 years to decode a human being, and at the
time that seemed reasonable.

Until this man, scientist, entrepreneur and speedboat enthusiast Craig
Venter, decided that he could do it faster, much faster.

J. CRAIG VENTER: It's like sailing. Once you have two sailboats on the
water going approximately in the same direction, they're racing. And science
works very much the same way. If you have two labs remotely working on the same
thing, one tries to get there faster, or better, higher quality,
something different, in part because our society recognizes only first
place.

ROBERT KRULWICH: Back in 1990, Venter was one of many
government scientists painstakingly decoding proteins and genes. His focus was
one protein in the brain.

J. CRAIG VENTER: It took ten years to get the protein and it took a
whole year to get 1000 letters of genetic code.

ROBERT KRULWICH: For Venter that was way too slow.

So you're sitting there thinking there must be a better way when you're
gazing out the window?

J. CRAIG VENTER: Yes, there had to be a better way.

ROBERT KRULWICH: And that's when he learned that someone had
invented a new machine that could identify Cs and Ts and As and Gs with
remarkable speed. And Craig Venter just loves machines that go fast.

J. CRAIG VENTER: I immediately contacted the company to see if I could
get one of the first machines.

ROBERT KRULWICH: And here's how they work. Human DNA is
chopped by robots into tiny pieces. These pieces are copied over and over again
in bacteria and then tagged with colored dyes. A laser bounces light off each
snip of DNA and the colors that it sees, represent individual letters in the
genetic code. And these computers can do this 24 hours a day, every
day.

J. CRAIG VENTER: So now you can see clearly the peaks.

ROBERT KRULWICH: Yup.

J. CRAIG VENTER: So there's just a blue one coming up so that's a C
coming up. You could read this and you could write this all down.

ROBERT KRULWICH: So blue, yellow, red, red,
yellow...

J. CRAIG VENTER: So that's C,G,T,T,A.

ROBERT KRULWICH: Then somehow all of these little pieces have
to be put together again in the right order. Venter's dream was to have
hundreds of new machines at his fingertips so he quit his government job and
formed a company he called Celera Genomics. Celera from the Latin word
celerity, meaning speed. And this is what he built.

ROBERT KRULWICH: So, who is this guy and why is he such a
bulldog for speed?

Craig Venter grew up in California, left high school and
spent a year as a surfing bum—on the beach by day and a stock boy at Sears by
night. He was, inevitably, drafted, went to Vietnam with the Navy. That's him
way over there on the left. He was eventually assigned to a Naval hospital in
Danang during the Tet offensive when Americans were taking very heavy
casualties. At 21, he was in the triage unit, where they decide who will live
and who will die.

When you're young and you see a lot of people die and they all could be
you, do you then feel that you sort of owe them cures? Cures that they'll never
get? Or am I over-romanticizing?

J. CRAIG VENTER: Well, the motivations become complex. That's certainly
a part of it. Also I think surviving the year there was...it sort of puts
things in perspective, I think. If you're not in that situation, you can never
truly have it in perspective.

ROBERT KRULWICH: You hear time...you hear ticking?

J. CRAIG VENTER: Yes. But also I feel that I've had this tremendous gift
for all these years since I got back in 1968, and I wanted to make sure I did
something with it.

ROBERT KRULWICH: In the spring of 1998, Venter announced that
he and his company were going to sequence all three billion letters of the
human genome in two years. Remember, the government said it would take
15.

J. CRAIG VENTER: There was a lot of arrogance that went with that
program. They were going to do it at their pace. And a lot of the scientists,
you know, if they were really being honest with you, would tell you that they
planned to retire doing this program. That's not what we think is the right way
to do science, especially science that affects so many people's lives.

ROBERT COOK-DEEGAN: Craig is a high testosterone male who has...he just
loves being an iconoclast. Right? He loves rattling people's cages and he's
done that consistently in the genome project.

ROBERT KRULWICH: Craig Venter's announcement that his team
would finish the entire genome in just two years galvanized everybody working
on the public project. Now they were scrambling to keep up.

HUMAN GENOME PROJECT STAFF MEMBER: There are some limitations. We don't
think we can get this thing to go any faster at the moment without throwing a
lot more robotics at it. The arm physically takes twenty seconds to...

ROBERT KRULWICH: Francis Collins, the head of the Human
Genome Project, was determined that Celera was not going to beat his teams
to the prize. He made a dramatic decision to try to cut five full years off the
original plan.

FRANCIS COLLINS: When the major Genome Centers met and agreed to go for
broke here, I don't think there was anybody in the room that was very confident
we could do that. I mean you could sit down with a piece of paper and make
projections, if everything went really well, that might get you there, but
there were so many ways this could have just run completely off the track.

ROBERT KRULWICH: At MIT they decided to try to scale up their
effort 15-fold and that meant a major change in their usual academic
pace.

LAUREN LINTON (MIT): We basically had a goal since March to get
to a plate-a-minute operation from womb to tomb all the way through.

ROBERT KRULWICH: In the fall of 1999, representatives from the
five major labs come to check out Eric Lander's operation. All the big honchos
in the Human Genome Project are here: scientists from Washington University in
St Louis, Baylor College of Medicine in Texas, the Department of Energy. She's
from the Sanger Center in England. If they want to finish the genome before
Craig Venter, these folks have to figure out how to outfit their labs with a
lot of new and fancy and unfamiliar equipment. And they've got to do it
fast.

ERIC LANDER: Since one's on the cutting edge...I guess they always call
it "the bleeding edge," right? Nothing really is working as you expect. All the
stuff we're doing will be working perfectly as soon as we're ready to junk
it.

ROBERT KRULWICH: The MIT crew is particularly excited about
their brand new three-hundred-thousand-dollar state-of-the-art DNA
purifying machine.

MIT STAFF RESEARCHER FOUR: Are you supposed to get the yellow light
right away?

ROBERT KRULWICH: I don't think the blinking light is a good
sign.

ERIC LANDER: It's sort of like flying a very large plane and repairing
it while you're flying. You want to figure out what went wrong. And you also
realize that you're spending, oh, tens of thousands of dollars an hour. So you
feel under a little pressure to sort of work this out as quickly as you
can.

ROBERT KRULWICH: So he calls the customer service line. And of
course he's put on hold. So he waits. And he waits. And he waits. Anyway, it
turns out that the three-hundred-thousand-dollar machine does have one tiny
little valve that's broken, and so it doesn't work.

ERIC LANDER: You never know whether the problem is due to some robot,
some funky little biochemistry, some chemical that you've got that isn't really
working. And so it's incredibly complicated.

MIT STAFF RESEARCHER FIVE: So we have a test transformation where we
transform a tenth of our ligation.

MIT STAFF RESEARCHER SIX: And add SDS to lyse the phage.

MIT STAFF RESEARCHER SEVEN: And all of our thermo-cyclers have
three-eighty-four-well plates.

MIT STAFF RESEARCHER EIGHT: So if you basically determine where your 96
well...plate wells were on this three hundred eighty-four-well plate and give
them each a different run-module...

FRANCIS COLLINS: When you try to ramp something up, anything that's the
slightest bit kludgy suddenly becomes a major bottleneck.

MIT STAFF RESEARCHER NINE: We talked about doing a full-up test today
and we weren't quite feeling good about doing that yet.

FRANCIS COLLINS: There was a considerable sense of white knuckles
amongst all of us, 'cause here we'd made this promise. We're on the record here
saying we're going to do this. And things weren't working. The machines were
breaking down. It's got to work now. The time is running out.

ROBERT KRULWICH: It took a while, but the government teams
finally hit their stride.

FRANCIS COLLINS: The fall of that year was really sort of the
determining time. The centers really proved their mettle. And every one of them
began to catch this rising curve and ride it. And we began to see data
appearing at prodigious rates. By early 2000, a thousand base pairs a second
were rolling out of this combined enterprise, seven days a week, 24 hours a
day, a thousand base pairs a second. Then it really starts to go.

ROBERT KRULWICH: And those thousands of base pairs poured out
of the university labs directly onto the Internet, updated every night. It's
available for anybody and everybody, including, by the way, the
competition.

Celera admits they got lots of data directly from the government. And Tony
White, who runs the company that owns Celera, says "Why not?"

TONY WHITE: That's publicly available data. I'm a taxpayer. Celera's a
taxpayer. You know, it's publicly...why should we be excluded from getting it?
I mean, again, are they creating it to give it to mankind except Celera? Is
that the idea? It isn't about us getting the data. It's about this academic
jealousy. It's about the fact that our data, in combination with theirs, gives
us a perceived, unfair advantage over this so-called "race."

ERIC LANDER: If they want to race us, that's their business.

ROBERT KRULWICH: Of course they do. Don't
they?

ERIC LANDER: I suppose they may.

ROBERT KRULWICH: I suspect strongly they may.

ERIC LANDER: Our job is to get that data out there so everybody
can go use it.

ROBERT KRULWICH: Since Celera was sequencing the genome with
private money, some critics wondered, "Why should the government put so much
cash into the exact same research?"

ERIC LANDER: In the United States, we invested in a national highway
system in the 1950s. We got tremendous return for building roads for free and
letting everybody drive up and down them for whatever purpose they wanted.
We're building a road up and down the chromosomes for free. People can drive up
and down those chromosomes for anything they want to. They can make
discoveries. They can learn about medicine. They can learn about history.
Whatever they want. It is worth the public investment to make those roads
available.

ROBERT KRULWICH: But wait a second - What I really want to
know is, if you are making a roadmap of a human being, which human beings are
we mapping? I mean, humans come in so many varieties, so whose genes exactly
are we looking at?

ERIC LANDER: It's mostly a guy from Buffalo and a woman from
Buffalo. That's because the laboratory...

ROBERT KRULWICH: Whoa, whoa. An anonymous couple from
Buffalo?

ERIC LANDER: No, they're not a couple. They're not a couple.
They've never met.

ROBERT KRULWICH: Oh, I see.

ERIC LANDER: The laboratory was a laboratory in Buffalo. And so
they put an ad in Buffalo newspapers and they got random volunteers from
Buffalo. They got about 20 of them, and chose at random this sample and that
sample and that sample. So nobody knows who they are.

ROBERT KRULWICH: And what about Celera? Whose DNA are they
mapping?

They also got a bunch of volunteers, around 20, and picked five lucky
winners.

J. CRAIG VENTER: We tried to have some diversity in terms of...we
had an African American, somebody of self-proclaimed Chinese ancestry, two
Caucasians and a Hispanic. And so some of the volunteers were here on the
staff, and...

ROBERT KRULWICH: I have to ask 'cause everybody does. Are you
one of them?

J. CRAIG VENTER: I am one of the volunteers, yes.

ROBERT KRULWICH: Oh. Do you know whether you, whether you are
one of the winners?

J. CRAIG VENTER: I have a pretty good idea, yes. Uh, but, I can't
disclose that. Because it doesn't matter.

ROBERT KRULWICH: Well if you're the head of the company and
you're watching the decoding of "moi," that has a little Miss Piggy quality to
it.

J. CRAIG VENTER: Well, any scientist that I know would love to be
looking at their own genetic code. I mean, how could you not want to and work
in this field?

ROBERT KRULWICH: Well, I don't know, I don't work in this
field. But I do wonder, could any small group, I mean, could that guy from
Buffalo, could he really be a stand-in for all human kind? Hasn't it been
drummed into us since birth that we are all different, each and every one of us
completely unique? We certainly look different. People come in so many shapes
and colors and sizes the DNA of these humans has got to be significantly
different from the DNA of this human. right?

ERIC LANDER: The genetic difference between any two people: one
tenth of a percent. Those two, and any two people on this planet are 99.9
percent identical at the DNA level. It's only one letter in a thousand
difference.

ROBERT KRULWICH: And if I were to bring secretly into another
room, a black man, an Asian man, and a white man, and show you only their
genetic code, could you tell which one was the white...?

ERIC LANDER: Probably not.

What's going on? Well, it tells us that, first, as a species we're very, very
closely related. 'Cause any two humans being 99.9 percent identical means that
we're much more closely related than any two chimpanzees in Africa.

ROBERT KRULWICH: Wait, wait. Wait, wait, wait, wait. You mean
if two Chimpanzees are swinging through the forest and you look at the genes of
Chimp A and the genes of Chimp B...

ERIC LANDER: Average difference between those chimps is four or
five times more than the average difference between two humans that you'd pluck
off this planet.

ROBERT KRULWICH: Because we're such a young
species?

ERIC LANDER: That's right. See, the thing is, we are the
descendants of a very small founding population. Every human on this planet
goes back to a founding population of perhaps 10 or 20 thousand people in
Africa about 100 thousand years ago. That little population didn't have a great
deal of genetic variation. And what happened was, it was successful. It
multiplied all over the world, but in that time relatively little new genetic
variation has built up. And so we have today on our planet about the same
genetic variation that we walked out of Africa with.

ROBERT KRULWICH: So people are incredibly similar to each
other. But not only that. It turns out we also share many genes
with...well...everything.

Fifty percent of the genes in a banana are in us?

ERIC LANDER: How different are you from a banana?

ROBERT KRULWICH: I feel...and I feel I can say this with some
authority...very different from a banana.

ERIC LANDER: You may feel different from a banana...

ROBERT KRULWICH: I eat a banana, but I have
never...

ERIC LANDER: Look, you've got cells, you've got to make those
cells divide. All the machinery for replicating your DNA, all the machinery for
controlling the cell cycle, the cell surface, for making nutrients—all that's
the same in you and a banana.

Deep down, the fundamental mechanisms of life were worked out only once on
this planet, and they've gotten reused in every organism. The closer and closer
you get to a cell the more you see a bag with stuff in it and a nucleus, and
most of those basic functions are the same. Evolution doesn't go reinvent
something when it doesn't have to.

Take baker's yeast. Baker's yeast we're related to one and a half billion
years ago. But even after one and a half billion years of evolutionary
separation, the parts are still interchangeable for lots of these genes.

ROBERT KRULWICH: Now, does that mean—I just want to make sure
if I understand this right. Does that mean when you look through those things
that all the Cs and the As and the Ts and the Ts and the Gs...are you seeing
the exact same letter sequences in the exact same alignment? When you look at
the yeast and you look at the person, is it C-C-A-T-T-T?

ERIC LANDER: Sometimes. It's eerie. The gene sequence is almost
identical. There are some genes, like ubiquitin, that's 97percent identical
between humans and yeast, even after a billion years of evolution.

ROBERT KRULWICH: Well, with a name like that it's got to
be.

ERIC LANDER: Well, yeah, but you've got to understand that deep
down we are very much partaking of that same bag of tricks that evolution's
been using to make organisms all over this planet.

ROBERT KRULWICH: It seems incredible but all this information
about evolution, about our relationship to each other and to all living things,
it's all right here in this monotonous stream of letters. And as the
Human Genome Project progressed and hit high gear the pace of discovery
quickened. Once they got fully automated, it wasn't long before Lander and
Collins and all the other public project teams had reason to
celebrate.

FRANCIS COLLINS: I'm Francis Collins, the director of the National Human
Genome Research Institute and we're happy to be here together to have a party
today.

ROBERT KRULWICH: By November of 1999, they had reached a major
milestone. In a five-way awards ceremony, hooked up by satellite, the
major university teams announced they had finished a billion base pairs of DNA,
a third of the total genome.

ERIC LANDER: Have we got everybody? I would like to propose a
toast. A billion base pairs, all on the public Internet, available to anybody
in the world. It's an incredible achievement. It hasn't been completely
painless. And because I know everybody in this room is living and breathing and
thinking every single moment in the day, about how to make all this happen, how
we can hit full scale I want to be sure you realize what a remarkable thing we
pulled off. I hope you also know that this is history. Whatever else you do in
your lives, you're part of history. We're part of an amazing effort on the part
of the world to produce this. And this isn't going to be like the moon, where
we just visit occasionally. This is going to be something that every student,
every doctor uses every day in the next century and the century after that.
It's something to tell your kids about. Something to tell your grandkids about.
It's something you should all be tremendously proud of. And I'm tremendously
proud of you. A toast to this remarkable group, to the work we've done, to the
work ahead. Hear, hear.

ROBERT KRULWICH: Everybody here is hoping the Genome Project
will help cure disease, and the sooner it's done, the better for all of us. But
there's something more than idealism, more than even pride that's driving this
race to finish the genome. And that is the knowledge that with every day that
passes more and more pieces of our genome are being turned into private
property by way of the US Patent Office.

PATENT OFFICE STAFF MEMBER: I say a property...

ROBERT KRULWICH: The office is inundated with requests for
patents for every imaginable invention, from Star Wars action figures, to jet
engines. And here along with all those gizmos, are requests for patents for
human genes, things that exist naturally in every one of us. How is this
possible?

TODD DICKINSON (Former Director, US Patent Office): We regard
genes as a patentable subject matter as we regard almost any chemical. We have
issued patents on a number of compounds, a number of compositions that are
found in the human body. For example the gene that encodes for insulin has been
patented. And that now is used to make almost all of the insulin that is made
so people's lives are being saved today. Diabetics' lives are better.

As a matter of fact if we ruled out every chemical that is found in the human
body, there would be an awful lot of inventions that would not be able to be
protected.

ROBERT KRULWICH: Generally, to patent an invention, you've got
to prove that it's new and useful. But a few years ago, critics said the patent
office wasn't being tough enough. So applicants would say, "Well, here's a
brand new sequence of As, Cs, Ts and Gs right out of our machines. That's new.
Now useful? What were they going to be used for? "Well, they were kind of vague
about use," says Eric Lander.

ERIC LANDER: The sort of thing that people used to do then was they
would say, "It could be used as a probe to detect itself." It's a trivial use.
I mean, it's like saying, "I could use this new protein as packing peanuts to
stuff in a box." I mean, it's true. It takes up space.

ROBERT KRULWICH: Wouldn't the patent examiner say, "That's not
useful."

ERIC LANDER: No, no, no. You see the patent guidelines are very unclear.
I don't object to giving somebody that limited-time monopoly when they've
really invented a cure for a disease, some really important therapy. I do
object to giving a monopoly when somebody has simply described a couple hundred
letters of a gene, has no idea what use you could have in medicine. Because
what's going to happen is you've given away that precious monopoly to somebody
who's done a little bit of work. And then the people who want to come along and
do a lot of work, to turn it into a therapy, well they've got to go pay the
person who already owns it. I think it's a bad deal for society.

ROBERT KRULWICH: It takes at least two years for the patent
office to process a single application, so right now, there are about 20,000
genetic patents waiting for approval. All of them are in limbo.

This can cause problems for drug companies who are trying to work with
genes to cure disease. I'm a company trying to do work on this, this, and this
rung of the ladder because I think I can maybe develop a cure for cancer right
here, just for the sake of argument. But of course I have to worry that
somebody owns this space.

ERIC LANDER: You have to worry a lot that this region here, that you're
working on, that might cure cancer has already been patented by somebody else
and that patent filing is not public. And so you're living with the shadow that
all of your work may go for naught.

ROBERT KRULWICH: Because one day the phone rings and
says "Sorry you can't work here. Get off my territory."

ERIC LANDER: That's right.

ROBERT KRULWICH: Or, "You can work here, but I'm going
to charge you $100,000 a week." Or "You can work here and I'll charge you a
nickel but I want 50 percent of whatever you discover or any of
it."

ERIC LANDER: And the problem here is...it's even worse
because many companies don't start the work whenever there's a cloud over who
owns what. If there's uncertainty...companies would rather be working someplace
where they don't have uncertainty. And therefore, I think work doesn't get done
because of the confusion over who owns stuff.

ROBERT KRULWICH: Supporters of patents say they're a crucial
incentive for drug companies. Drug research is phenomenally expensive, but if a
company can monopolize a big discovery with a patent, it can make hundreds of
millions of dollars.

Research scientists suddenly find themselves in an unfamiliar world ruled
by big money.

SHELDON KRIMSKY (Science Policy Analyst, Tufts
University): Every scientist who does research is now being looked upon
as a generator of wealth, even if that person is not interested in it. If they
sequence some DNA, that could be patentable material. So whether the scientist
likes it or not, he or she becomes an entrepreneur just by virtue of doing
science.

ROBERT KRULWICH: Craig Venter is first a scientist, but he has
made the leap from academia into the business world. Let me talk about the
business of this. Do you consider yourself a businessman?

J. CRAIG VENTER: No. In fact I still sort of bristle at the term
for some reason. But my philosophy is we would not get medical breakthroughs in
this country at all if it wasn't done in a business setting. We would not have
new therapies if we didn't have a biotech and pharmaceutical industry.

ROBERT KRULWICH: But are they...if you bristle at the word
businessman, that might be because in some part of your soul, you may think
that the business of science and the business of business are fundamentally
incompatible for one simple reason—that the business has to sell something and
the science has to learn or teach something.

J. CRAIG VENTER: I think I bristle at it because it's used as an
attack, used as a criticism. In this case, if the science is not spectacular,
if the medicine is not spectacular, there will be no profits.

ROBERT KRULWICH: Venter was given three hundred million
dollars to set up Celera, and his investors are expecting something in return.
But how can they profit from the genome?

At the moment, the company is banking on pure computer power. This is
Celera's Master Control. Twenty-four hours a day, technicians monitor all the
company's major operations, including the hundreds of sequencers that are
constantly decoding our genes.

And they oversee Celera's main source of income, a massive Website where,
for a fee, you can explore several genomes, including those of fruit flies,
mice and of course, humans. What all this adds up to is something like a big
browser, a user-friendly interface between you and your genes.

TONY WHITE (CEO, Applera Corporation): Our business is to
sell products that enable research. That's essentially what we do. So we're
used to selling the picks and the shovels to the miners. Tools to interpret the
human genome and other related species are merely more products along the same
genre. They just happen to be less tangible than a machine.

ROBERT KRULWICH: So Celera's business plan is to gather
information from all kinds of creatures, put it together and sell their
findings to drug companies or universities or whomever. But it's the selling
part, selling scientific information, that makes some scientists very
uncomfortable.

SHELDON KRIMSKY: This is a big change in the ethos of the scientific
community, which is supposedly...it was built upon the idea of communitarian
values of the free and open exchange of information. The fundamental idea that
when you learn something, you publish it immediately, you share it with others.
Science grows by this communitarian interest of shared knowledge.

TONY WHITE: I think, "Why doesn't Pfizer give away their drugs? They
could help a lot more people if they didn't charge for them."

CELERA STAFF MEMBER: At what point is free really free?

ROBERT KRULWICH: Tony White has absolutely no problem with
making money from the human genome.

TONY WHITE: I hope we have a legal monopoly on the information. I hope
our product is so good, and so valuable to people, that they feel that it's
necessary to come through us to get it.

Anybody who wants to can build all the tools that we're going to build.
Whether or not they will choose to is a different matter.

ROBERT KRULWICH: Now which is the better business to be
in, do you think, the landlord business, or this, "You subscribe, and I'll give
you some information about anything you want," business?

ERIC LANDER: They're both lousy businesses.

ROBERT KRULWICH: They're lousy?

ERIC LANDER: They're lousy businesses by comparison with the real
business. Make drugs. Actually make molecules that cure people.

ROBERT KRULWICH: Curing people is the whole point, right?

But if there is one thing that the Human Genome Project has taught
us, it's that finding cures is a whole lot harder than simply reading letters
of DNA.

Take, for example, the case of little Riley Demanche. At two months, Riley
appears to be a perfectly healthy baby boy. But he's not. When Riley was just
13 days old, Kathy Demanche got the call that every parent dreads.

KATHY DEMANCHE (Mother of a son with cystic fibrosis): My
pediatrician called on a Thursday evening and he said, "I need to talk to you
about the baby." He said, "Are you sitting down?" And I'm like, "Yeah." And
that really surprised me. And he said, "Are you holding the baby?" Because he
didn't want me to drop the baby, obviously. And he said, "The tests came
through, and Riley tested positive to cystic fibrosis."

And I was in shock.

ROBERT KRULWICH: As Kathy and her husband would soon
learn, cystic fibrosis, CF for short, attacks several organs of the body, but
especially the lungs. Its victims suffer from chronic respiratory infections.
Half of all CF patients die before the age of 30.

DAVID WALTZ (Children's Hospital, Boston): Sounds good.

KATHY DEMANCHE: Good.

DAVID WALTZ: I think we can be hopeful that their child will grow up to
have a normal and healthy, happy and long life. But at the present time, I
don't have any guarantees about that.

KATHY DEMANCHE: Someone had asked me, "Are you prepared to bury your son
at such a young age? Whether it's four or forty?" And he was 17 days old when
that happened. And I said, "I've had him for 17 days. I wouldn't trade those 17
days."

ROBERT KRULWICH: Finding the genetic defect that causes
CF was big news back in 1989.

TAPE OF NEWS ANCHOR: Medical researchers say they have discovered the
gene which is responsible for cystic fibrosis, the most common inherited fatal
disease in this country.

TAPE OF ROBERT DRESSING: We are going to cure this disease.

ROBERT KRULWICH: A lot of people expected the cure to
arrive any day. It didn't.

Francis Collins, now head of the government's Genome Project, led one of
the teams that discovered the CF gene.

FRANCIS COLLINS: We still have not seen this disease cured or even
particularly benefited by all of this wonderful molecular biology. CF is still
treated pretty much the way it was 10 years ago. But that is going to
change.

ROBERT KRULWICH: The original hope was that babies like
Riley could be cured by gene therapy, medicine that could provide a good
working copy of a broken gene. But attempts at gene therapy have hardly ever
worked. They remain highly controversial. So if there's going to be an
effective treatment for Riley, instead of fixing his genes, we're going to take
a look—and this is new territory—at his proteins.

ROBERT KRULWICH: What do proteins do?

J. CRAIG VENTER: When you look at yourself in the mirror, you don't see
DNA. You don't see RNA. You see proteins and the result of protein action. So
that's what we are physically composed of.

ROBERT KRULWICH: So it's not a Rogers and Hammerstein thing,
where one guy does the tune and the other guy does the lyrics. This is a case
where the genes create the proteins and the proteins create us?

J. CRAIG VENTER: That's right. We are the accumulation of our
proteins and protein activities.

ROBERT KRULWICH: A protein starts out as a long chain
of different chemicals, amino acids. But unlike genes, proteins won't work in
a straight line.

FRANCIS COLLINS: Genes are effectively one-dimensional. If you write
down the sequence of A, C, G, and T, that's kind of what you need to know about
that gene. But proteins are three-dimensional. They have to be because we're
three-dimensional and we're made of those proteins. Otherwise, we'd all sort of
be linear, unimaginably weird creatures.

ROBERT KRULWICH: Here's part of a protein. Think of
them as tangles of ribbon. They come in any number of different shapes.
They can look like this. Or like this. Or this. The varieties are
endless.

But when it's created, every protein is told, "Here is your shape." And
that shape defines what it does, tells all the other proteins what it does. And
that's how they recognize each other when they hook up and do business. In the
protein world, your shape is your destiny.

FRANCIS COLLINS: They have needs and reasons to want to be
snuggled up against each other in a particular way. And actually a particular
amino acid sequence will almost always fold in a precise way.

ROBERT KRULWICH: Should I think origami-like? I mean,
should I think folding and then...

FRANCIS COLLINS: It's very elegant, very complicated. And we still do
not have the ability to precisely predict how that's going to work. But
obviously it does work.

ROBERT KRULWICH: Except, of course, if something does
go wrong. And that's what happened to baby Riley. Riley has an tiny error in
his DNA. Just three letters out of three billion are missing. But because of
that error, he has a faulty gene. And that faulty gene creates a faulty, or
misshapen protein. And just the slightest little changes in shape and boom. The
consequences are huge.

Because it is now misshapen, and a key protein that is found in lung
cells, in fact in many cells, can't do its job.

So let's take a look at some real lung cells. We'll travel in.

This is the lining, or the membrane, of a lung cell and here is how the
protein is supposed to work. The top of your screen is the outside of a cell;
the bottom of the screen, the inside of the cell, of course. And our healthy
protein is providing a kind of chute so that salt can enter and leave the cell.
Those little green bubbles, that's salt. And as you see here, the salt is
getting through.

But if the protein is not the right shape, then it's not allowed into the
membrane. It can't do it's job. And without that protein, as you see here, salt
gets trapped inside the cell. And that triggers a whole chain of reactions that
makes the cell surface sticky and covered with thick mucus. That mucus
has to be dislodged physically.

Riley's family is learning to loosen the mucus that may develop in his
lungs, and fight infections with antibiotics. But what the doctors and the
scientists would love to do is, if they can't fix baby Riley's genes, then
maybe there's some way to treat Riley's misshapen protein and restore the
original shape. Because if you could just get them shaped right, the proteins
should become instantly recognizable to other proteins and get back to
business.

But look at these things. How would we ever learn to properly fold wildly,
multi-dimensional proteins? It may be doable, but it won't be easy.

ERIC LANDER: The genome project was a piece of cake
compared to most other things, because genetic information is linear. It goes
in a simple line up and down the chromosome. Once you start talking about the
three-dimensional shapes into which protein chains can fold and how they can
stick to each other in many different ways to do things, or the ways in which
cells can interact, like wiring up in your brain, you're not in a
one-dimensional problem anymore. You're not in Kansas anymore.

ROBERT KRULWICH: And as scientists head into the world
of proteins, they're looking very closely at patients like Tony
Ramos.

Tony has cystic fibrosis, but it's not the typical case. CF almost always
develops in early childhood. Tony didn't have any symptoms until she was 15.

TONY RAMOS (Cystic fibrosis patient): I started having a cough.
And then we kept thinking I was catching a lot of colds. And my stepmother
thought, "That's not right." So I started going to doctors trying to figure it
out and went through a lot of tests because I don't fit the profile.
Tuberculosis, walking pneumonia, you know, test after test.

ROBERT KRULWICH: At the time of her diagnosis, Tony's
family was told she might not survive beyond her twenty-first birthday. She is
now in her mid-forties, but her CF is worsening. Two or three times a year, she
does have to be admitted to the hospital to clean out her lungs.

TONY RAMOS: They were always doing some little funky study to
help the cause because we're not the normal...you know...there's not a whole
lot of us. I know that they don't know why. And it's the big question mark. And
hopefully, research will keep going to figure it out.

ROBERT KRULWICH: Here's the question. Tony was born
with a mistake in the same gene as baby Riley, and yet, for some reason, when
Tony was a baby she didn't get sick. Why? And now that she is sick, she hasn't
died. Why? What does Tony have that the other CF patients don't
have?

Dr. Craig Gerard believes the answer lies in her genes, in her
DNA.

CRAIG GERARD (Children's Hospital, Boston): No gene acts in
isolation. It is always acting as a part of a larger picture. And there can
therefore be other genes which compensate.

ROBERT KRULWICH: Could it be that Tony has some other
genetic mutations, good mutations that are producing good proteins that kept
her healthy for 15 years? That are keeping her alive right
now?

CRAIG GERARD: In my opinion there are genes that are allowing her to
have a more beneficial course, if you will, than another patient.

ROBERT KRULWICH: Dr. Gerard is searching for the special
ingredient in Tony. If it turns out she has one or two good proteins that are
helping her, maybe we could bottle them and use them to help all CF patients
like baby Riley.

No one can predict Riley's future, or to what extent CF will affect his
life. But now that we're getting the map of our genes, we'll be able to take
the next big step.

Because what genes do, basically, is they make proteins.

I get the sense that everybody is getting out of the gene
business and suddenly going into this new business I hear about, called the
protein business. There's even a new name, instead of genome, I'm hearing this
other name...

ERIC LANDER: The proteome.

ROBERT KRULWICH: The proteome. What's that?

ERIC LANDER: Well, the genome is the collection of all your genes
and DNA. The proteome is the collection of all your proteins. See, what's
happening is we're realizing that if we wanted to understand life, we
had to start systematically at the bottom and get all the building blocks. The
first building blocks are the DNA letters. From them we can infer the genes.
From the genes, we can infer the protein products that they make that do all
the work of your cell. Then we've got to understand what each of those proteins
does, what its shape is, how they interact with each other, and how they make
kind of circuits and connections with each other. So in some sense, this is
just the beginning of a very comprehensive, systematic program to understand
all the components and how they all connect with each other.

ROBERT KRULWICH: All the components and how they
connect? But how many components are there? How many genes and how many
proteins do we have?

ERIC LANDER: The real shock about the genome sequence was that we
have so many fewer genes than we've been teaching our students. The official
textbook answer is, "The human has 100,000 genes." Everybody's known that since
the early 1980s. The only problem is it's not true. Turns out we only have
30,000 or so genes.

ROBERT KRULWICH: Thirty thousand genes? That's it? Not
everybody agrees with this number but that's about as many as a mouse! Even a
fruit fly has 14,000 genes.

ERIC LANDER: That's really bothersome to many people, that we only have
about twice as many genes as a fruit fly, because we really like to think of
ourselves as a lot more than twice as complex.

ROBERT KRULWICH: Well, don't you?

ERIC LANDER: I certainly like to think of myself that way. And so
it raises two questions. Are we really more complex?

ROBERT KRULWICH: You show me the fruit fly that can
compose like Mozart, and then I'll obviously...

ERIC LANDER: Yeah, well, show me the human that can fly, right?
So?

ROBERT KRULWICH: All right.

ERIC LANDER: We all have our talents, right?

ROBERT KRULWICH: I suppose we do. But as it happens, we
have lots of genes that are virtually identical in us and fruit flies. But
happily, our genes seem to do more.

So, let's say that I am a fruit fly. One of my fruit fly genes may make one
and two slightly different proteins. But now I'm a human, and the
very same gene in me might make one, two, three, four different proteins. And
then these four proteins could combine and build even bigger and more
proteins.

ERIC LANDER: Turns out that the gene makes a message, but the
message can be spliced up in different ways. And so a gene might make three
proteins or four proteins, and then that protein can get modified. There could
be other proteins that stick some phosphate group on it, or two phosphate
groups. And in fact all of these modifications to the proteins could make them
function differently. So, while you might only have, say 30,000 genes, you
could have 100,000 distinct proteins. And when you're done putting all the
different modifications on them, there might be a million of them. Scary
thought.

ROBERT KRULWICH: So, starting with the same raw
ingredients, the fruit fly goes, "hm, phht, hm, phht, hm, phht," but the human,
by somehow or other being able to arrange all the parts in many different ways,
can produce melodies perhaps.

ERIC LANDER: Yes. Although we're not that good at hearing the
melodies yet. We can...one of the exciting things about reading the genome
sequence now is we're getting a glimpse at that complexity of the parts, and
how it's a symphony rather than a simple tune. But it's not that easy to just
read the sheet music there and hear the symphony that's coming out of
it.

ROBERT KRULWICH: Okay, so it's not just the number of
genes, it's all the different proteins they can make and then the way
those proteins interact. And to figure out all those interactions and
how they affect health and disease, that's going to keep scientists very busy
for the next few decades.

But of course, before the research can begin in earnest, they first have to
complete the parts list—all the genes.

And by the spring of 2000, both sides—the public labs and
Celera—they were in hyperdrive—each camp madly trying to be the first
to reach the finish line and get all three billion letters.

GENE MYERS (Vice President, Informatics Research, Celera): The
pace of things and the magnitude of things was really incredible. I mean, I
would remember coming in and just having this really gripping feeling in my
gut, I mean just an intense kind of, "Oh, my God. Am I up to this?"

ROBERT COOK-DEEGAN: You know, whoever has this reference sequence of the
Human Genome out there in the world first, they're going to be famous. They're
going to be on the front page of the New York Times and a lot more than that,
for a long time. They're going to be, you know, celebrities. And you know, when
that's going on, it's not unreasonable that people are going to reach for that
star and try to get there before the other person.

TONY WHITE: I thought the really intense competition in this world was
among businesses where there was a profit motive. I now find that we are pikers
in the business world, compared to the academic competition that exists out
there. And I'm beginning to understand why. Because their currency is
publication. Their currency is attribution. And their next funding comes from
their last victory.

ROBERT COOK-DEEGAN: I think we're all better off for the fact that there
is this competition. What you want is a system that gets people riled up
and trying to do something faster, better and cheaper than the next
guy.

GENE MYERS: The environment at Celera was really intense, and it
reminded me of finals week at Cal Tech. And there's a tradition at Cal Tech
that on the very first day of finals week, The Ride of the Valkyries is
played at full blast. And so, I thought, "Well, since every week feels like
it's finals week here, why don't I play The Ride, and see what
happens."

So we got a whole bunch of Viking hats and we end up buying Nerf® bows,
okay? Since we're Nordic Valkyrians. And the next week, we're shooting each
other. And we go, "You know, there's something not right about this." So we
decided the next week that we'd start doing raiding parties, then raid some
of the other teams.

Unbeknownst to us, they had been preparing themselves. They had little beanie
hats. Okay, and their own Nerf® weapons. Then the war started.

It's just a release. It's a way of kind of dealing with the pressure, I think.
We all ran around like crazy for five or ten minutes, and got a little
physical exercise, and had a few laughs. And then we're ready to really go
after it.

ROBERT KRULWICH: The Wagner seems to be working.

Output at Celera continues at a relentless pace. Venter insists that the
urgency stems not only from a desire to beat the government project, but the
firm belief that what's coming out of these machines—all the As, Cs, Ts, and
Gs—will have a profound impact on all our lives.

J. CRAIG VENTER: It's a new beginning in science and until we get all
that data, that can't really take place. Anybody that has cancer, anybody that
has a family member with a serious disease...this data and information offers
them tremendous hope that things could change in the future.

ERIC LANDER: In the past, if you wanted to explain diabetes, you always
had to scratch your head and say, "Well, it might be something else we've never
seen before." But knowing that you've got the full parts list radically changes
biomedical research, because you can't wave your hands and say, "It might be
something else." There is no something else.

ROBERT KRULWICH: In the past, finding the genes that
cause a disease was a painstakingly slow process. But with the completion of a
list, it should be much easier to make a direct connection from disease to
gene.

But how? Well, let's say I'm looking for a gene that causes
something...we'll make it male-pattern baldness. How would I go about
that?

Well, I'd want to get a bunch of bald guys.

So here are three bald guys and take their blood and look at their DNA.
Now, I'll take three guys with lots of hair, and here's their DNA. And
what if the bald guys all share a particular spelling right here, in this spot,
which we call the bald spot. And at the same spot, you notice the hairy
guys have...you see that? A different spelling.

So is this the gene that causes baldness? Maybe, but probably not. This
could be a coincidence

So, how do I improve my chances of finding the specific spelling difference
that relates to baldness? It would help if I knew that the bald guys and the
hairy guys had really similar DNA, except for the genes I suspect may
make them either bald or hairy.

Where do I find guys who are very, very similar, with a few exceptions? A
family, right? If there were brothers and fathers and sons and cousins, for
instance, who share lots of genes. So let's say these three guys are
brothers—astonishing similarity really in the face. But notice that one
of them is hairy and two are bald.

Whatever is making this one different should stand out when you compare
their genes. And the same for these guys. There's a difference, clearly, in the
photos, but that difference may turn up in the genes.

You could do the same thing for any disease you like. So, if
I could comb through the DNA of lots of people who are related, and I find
some of them are sick and some of them are healthy, I
might have a much better chance of figuring out which genes are
involved.

But where do I do this? Well, one place is a little island
nation in the North Atlantic, Iceland. In many ways, Iceland is the perfect
place to look for genes that cause diseases. It's got a tiny population, only
about 280,000 people, and virtually all of them are descended from the original
settlers—Vikings who came here over 1000 years ago.

KARI STEFANSSON (President, deCODE Genetics): If you drive around
this country you will have great difficulty finding any evidence of the dynamic
culture that was here for almost 1100 years. There are no great
buildings.There are no monuments.

ROBERT KRULWICH: But one thing Iceland does have is a
fantastic written history, including almost everybody's family tree. And now
it's all in a giant database. Just punch in a social security number and there
they are, all your ancestors, right back to the original Viking.

THORDUR KRISTJANSSON (deCODE Genetics): So what we have here is
my ancestor tree. I'm here at the bottom. This is my father and mother, my
grandparents,great grandparents, and so on. We can find an individual
that was one of the original settlers of Iceland. Here we have Ketill
Bjarnarson, called Ketill Flatnefur, meaning he had a flat nose, so he may have
broken it in a fight or something. And we estimate that he was born around the
year 805.

ROBERT KRULWICH: Kari Stefansson is a Harvard-trained
scientist who saw the potential gold mine that might be hidden in Iceland's
genetic history. He set up a company called deCODE Genetics to combine
age-old family trees with state-of-the-art DNA analysis and computer
technology, and systematically hunt down the genes that cause
disease.

KARI STEFANSON: Our idea was to try to bring together as much data on
health care as possible, as much data on genetics as possible, and the
genealogy, and simply use the informatics tools to help us to discover new
knowledge, discover new ways to diagnose, treat and prevent diseases.

ROBERT KRULWICH: One of deCODE's first projects was to
look for the genes that might cause osteoarthritis. Regnheidir
Magnusdottir had the debilitating disease most of her life.

(Translation of) REGNHEIDIR MAGNUSDOTTIR (Arthritis patient): The
first symptoms appeared when I was 12. And by the age of 14, my knees hurt very
badly. No one really paid any attention. That's just the way it was. But by the
age of 39, I'd had enough, so I went to a doctor.

ROBERT KRULWICH: Mrs. Magnusdottir was never alone in
her suffering. She's one of 17 children. Eleven of them were so stricken with
arthritis, they had to have their hips replaced. This was exactly the kind of
family that deCode was looking for.

They got Mrs. Magnusdottir and other members of her family to donate blood
samples for DNA analysis. And to find more of her relatives, people she'd
never met, deCode just entered her social security number into their giant data
base, and there they were.

But which of these people have arthritis? To find out, Stefansson asked the
government of Iceland to give his company exclusive access to the entire
country's medical records. And in exchange, deCode would pay a million dollars
a year plus a share of any profits. That way, deCODE could link everything in
their computers—DNA, health records and family trees.

KARI STEFANSSON: This idea was probably more debated than any
other issue in the history of the Republic. On the eve of the Parliamentary
vote on the bill there was an opinion poll taken which showed that 75
percent of those that took a stand on the issue supported the passage of the
bill; 25 percent were against it.

ROBERT KRULWICH: Among that 25percent against the plan were
most of Iceland's doctors.

TOMAS ZOEGA (Icelandic Medical Association): I felt there was
something fundamentally wrong in all of this, you know? They do know everything
about you, not only about your medical history, about your medical past, but
they now do have your gene, the DNA. They know about your future, something
about your children, about your relatives.

BJORN GUNDMARSSON (Havmnar Health Center): We find ourselves
paralyzed because there is really nothing we can do, because the one who takes
the responsibility, is the management of the health center. If they give away
this information from the medical records they get money. And everybody needs
money. Healthcare really needs money.

ROBERT KRULWICH: So what's really the problem here? Well let's
take a hypothetical example. I'm going to make all this up. Let's pretend
these are medical records of an average person. And we'll suppose that right
here I see an HIV test, and then over here is medication for anxiety
after what appears to be a messy divorce, and over here a parent who died of
Alzheimer's.

Now, this is all stuff that could happen to anybody, but do
you want it all in some central computer bank? And do you want it linked in
the same computer to all your relatives and to your own personal DNA
file? And should anybody have the right to go on a fishing expedition through
your medical history and your DNA?

Well, it may be frightening, but it also might work. deCODE claims it has
discovered several genes that may contribute to osteoarthritis. So this
approach, combining family trees, medical records and DNA could lead to better
drugs, or to cures for a whole range of diseases.

KARI STEFANSSON: To have all of the data in one place so you can use the
modern informatics equipment to juxtapose the bits and pieces of data and look
for the best fit, is an absolutely fascinating possibility.

ROBERT KRULWICH: Stefansson says no one's forced to do this, and there are elaborate privacy protections in place: no names are used and social security numbers are encoded. He also argues that the DNA part of the database is voluntary.

KARI STEFANSSON: The healthcare database only contains healthcare
information. We can cross-reference it with DNA information but only from those
individuals who have been willing to give us blood, allowing us to isolate DNA,
genotype it and cross-reference it with the database. Only from those who have
deliberately taken that risk. So it's not imposed on anyone, and no one who is
scared of it, no one who is really afraid of it, should come and give us
blood.

ROBERT KRULWICH: DNA databases are popping up all over
the world, including the U.S. They all have rules for protecting privacy, but
they still make ethicists nervous.

GEORGE ANNAS (Boston University): I like to use the analogy of
the DNA molecule to a future diary—there's a lot of information in a DNA
molecule. The reason I call it a diary, a future diary, is because I think it's
that private. I don't think anybody should be able to open up your future diary
except you.

ROBERT KRULWICH: One rather bleak vision of where all
this could lead is presented in the Hollywood film "Gattaca." This is a world
where everybody's DNA, everybody's future diary, is an open book. Everyone who
can afford it has their children made to spec. But what happens to the poor
slob who was conceived the old-fashioned way?

GATTACA VOICEOVER: "I'll never understand what possessed my
mother to put her faith in God's hands rather than those of her local
geneticist. Ten fingers, ten toes, that's all that used to matter. Not
now. Now, only seconds old, the exact time and cause of my death was already
known."

ROBERT KRULWICH: Thirty point two years. The nurse
seems to know precisely what's going to happen to this baby. Which is
ridiculous, right? Never happen. Or is it possible that one day we will be able
to look with disturbing clarity into our future? Ten, twenty, even seventy
years ahead?

GEORGE ANNAS: That is one possible future—where this becomes so routine
that at birth, everybody gets a profile. It goes right to their medical record.
One copy goes to the FBI so we have an identification system for all possible
crimes in the United States. One copy goes...where? To the grade school? To the
high school? To the college? To the employer? To the military? Like, a horrific
future. Although I have to say there are many in the biotech industry
and the medical profession who think that's a terrific future.

ROBERT KRULWICH: In fact, a lot of the technology
already exists, now, today.

These guys in the funny suits are making gene chips. The little needles are
dropping tiny, nearly invisible bits of DNA onto glass slides. And where did
the DNA come from? From babies. Thousands of them.

Each chip can support eighty thousand different DNA tests.

MARK SCHENA (Stanford University): So a single chip, in
principle, will allow you to test, say, 1000 babies for 80 different human
diseases. So within a few minutes you can have a readout for thousands or even
tens of thousands of babies in a single experiment.

ROBERT KRULWICH: Already babies are routinely tested
for a handful of diseases. But with gene chips, everybody could be tested for
hundreds of conditions.

MARK SCHENA: Knowing is great. Knowing early is even better. And that's
really what the technology allows us to do.

ROBERT KRULWICH: Well, taking a test and knowing is
great for the baby or anybody really, as long as there's something you can do
about it. But think about this, because sometimes there may be a test but it
might take 20 years or 50 years...50 years to find a cure. So you could
take the test and you could learn that there is a disease coming
your way but you can't do a thing about it. Do you still want to know?

Or you could take the test, but the test won't say that you're going
to get the disease, it will simply say that you may get a
disease. And as you know there's a big difference between" you will" and "you
may."

Lissa Kapust and Lori Seigel are sisters who shared the wrenching
experience of cancer in the family. Way back there were three sisters. And then
in 1979 the youngest of the three, Melanie, was diagnosed with ovarian
cancer.

LISSA KAPUST (Sister of ovarian cancer patient): When my sister
was diagnosed, my response was disbelief. She was 30 years old. And I'd never
known anybody of that age to have ovarian cancer.

ROBERT KRULWICH: Melanie fought her cancer for four
years, but died in 1983. It seemed an isolated piece of bad luck. But then,
just about a year later Lissa discovered she had breast cancer. She was only
34. But the cancer hadn't spread, so the long-term outlook seemed
optimistic.

LISSA KAPUST: I actually had a radiation therapist who was tops in the
field, wrote many books on breast cancer and was very optimistic. And what I
remember him saying is that he and I would grow old together.

ROBERT KRULWICH: And Lissa was fine for 12 years. Then
she found another lump in the same breast.

LISSA KAPUST: It was the worst fear come true. The first time I could
hold on to hope. The second time, nobody was talking with me about
living to be old.

ROBERT KRULWICH: When Lissa discovered her second
cancer in 1996, scientists were just beginning to work out the link between
breast and ovarian cancers that run in families. Mary-Claire King was one of
the scientists who discovered that changes or mutations in two specific genes
make a woman's risk of breast and ovarian cancer much higher.

The genes are called BRCA 1 and 2.

MARY-CLAIRE KING (University of Washington): BRCA 1 and BRCA 2
are perfectly healthy, normal genes that all of us have, but in a few
families mutations in these genes are inherited.

ROBERT KRULWICH: So in a normal gene—see we're going
to spell it out for you here letter by letter—this is the normal sequence
ending G T A G C A G T. Now we're going to make a copy; now we're going to lose
two of the letters, just two and then...see? Watch them shift over. Do you see
that? This new configuration is a mutation which can often cause breast
cancer.

MARY-CLAIRE KING: In the United States and Western Europe and Canada,
the risk of developing breast cancer for women in the population as a whole is
about 10 percent over the course of her lifetime, with, of course, most of that
risk occurring later in her life. For a woman with a mutation in BRCA 1 or BRCA
2, the lifetime risk of breast cancer is about 80 percent. It's very
high.

ROBERT KRULWICH: Right around the time of Lissa's second bout
of breast cancer, a test for BRCA mutations became available. Lissa and her
sister Lori decided to be tested.

LORI SIEGEL (Sister of ovarian cancer patient): I do remember the
day that I went to find out the results. Panic. Terror. I mean, what was
I going to find out? Talking about, you know, the blood surging through your
temples. I mean I just remember sheer terror.

ROBERT KRULWICH: Turns out Lori was fine. But Lissa
discovered that she does carry a BRCA mutation. It is not easy waking up
every morning wondering if today is the day you may get sick.

DOCTOR: Any questions about the results from the biopsy from
April?

LISSA KAPUST: No questions about the results. Again it feels like
often my life is dodging bullets.

ROBERT KRULWICH: With the second cancer, Lissa had her right
breast completely removed and then another operation to take out her ovaries.

NURSE: Okay, just keep a tight fist until I'm in.

ROBERT KRULWICH: She also has a high risk of cancer in
her left breast. BRCA mutations are relatively rare and only cause maybe five
or ten percent of all breast cancer. But knowing that there's a BRCA
mutation in the family affects everybody.

ERIC KAPUST: The gene doesn't go away. The time passed since the last
cancer doesn't buy you the safety. And the consequences run through the family.
I suppose that for my daughter, who yet has not shown any significant impact of
this, the knowledge that there's a genetic component that she can't deny will,
I'm sure, color her life in serious ways.

ROBERT KRULWICH: Lissa's son, Justin, is 21. Her
daughter, Alanna, is 18. There is a fifty-fifty chance that each of them has
inherited the BRCA mutation from Lissa. The only way to know would be to take a
test. And when should they do that? When is the right time?

ALANNA KAPUST (Daughter of breast cancer patient): I actually
never really thought about it until biology this year, when my teacher posed a
hypothetical, supposedly, question to people, saying, "What would you do? Can
you imagine what you would do, if you were faced with the situation where you
knew that you might have this disease that would be deadly. Or it would cause
you to be sick and you could do a test that you could find out whether or not
you had it?" And I was sitting there in class saying, "Maybe it's not so
hypothetical."

ROBERT KRULWICH: And then, in her senior year of high
school, Alanna felt a lump in her own breast.

ALANNA KAPUST: I did have the whole, "Oh it can't be happening to me.
Not yet," kind of thing. I mean, I have the reservation in the back of
my mind that eventually it may very well happen to me and if it does, then
I'll fight it then. I'll deal with it then. But I don't expect...or I
definitely didn't expect for this to be happening to me when I was 17 years
old.

ROBERT KRULWICH: Alanna's lump was not cancer. And for
now she doesn't want the test. Because if she knew that she had the bad
gene, she'd only have two options: the choice of removing her breasts and
ovaries to try to reduce her risk or just to be closely monitored and
wait.

LISSA KAPUST: She's followed every year. Seems a little young to, you
know, have her...to have to face that. On the other hand, it also feels like
the belt and suspenders technique, we just have to do everything we can
do.

ROBERT KRULWICH: In the next 20 years, this family's
predicament will become more and more common as more and more genes are linked
to more and more diseases and more tests become available. But we will
all have to ask, "Do we want to know?" And when we know, can we live with an
answer that says maybe, but maybe not?

LISSA KAPUST: Driving home from work today, I was tuned in to public
radio and there was a professor of astronomy talking about a brand new
telescope to look into the galaxies. And they're calling it the equivalent of
the Human Genome Project. And I was thinking, "Hmm, not quite the equivalent of
the Human Genome Project." Because it's without some of the ethical, moral
angst—real people issues where it's a bit of a roller coaster ride between,
you know, "This is going to hold answers, and hope, and treatments, and
interventions, and cure." Versus, "It's not clear what this all means."

ROBERT KRULWICH: And if things aren't clear now, what
about the future, when we may not only cure disease, but do so much
more?

GATTACA GENETIC COUNSELOR: "Your extracted eggs, Marie,
have been fertilized with Antonio's sperm. You have specified hazel eyes, dark
hair and fair skin. All that remains is to select the most compatible
candidate. I've taken the liberty of eradicating any potentially prejudicial
conditions: premature baldness, myopia, alcoholism, obesity, et cetera."

GATTACA MOM: "We didn't want...I mean...diseases...yes,
but..."

GATTACA DAD: "Right. And we were just wondering if it was
good to leave a few things to chance."

GATTACA GENETIC COUNSELOR: "You want to give your child the best
possible start. And keep in mind this child is still you, simply the best of
you. You could conceive naturally a thousand times and never get such a
result."

FRANCIS COLLINS:Gattaca really raised some interesting points.
The technology that's being described there is, in fact, right in front of us
or almost in front of us.

ROBERT KRULWICH: That seems to me almost extremely likely to
happen, because what parent wouldn't want to introduce a child that wouldn't
have...at least be where all the other kids could be?

FRANCIS COLLINS: That's why the scenario is chilling. It portrayed a
society where genetic determinism had basically run wild. I think society in
general has smiled upon the use of genetics for preventing terrible diseases.
But when you begin to blur that boundary of making your kids genetically
different in a way that enhances their performance in some way, that starts to
make most of us uneasy.

ROBERT KRULWICH: What if we lived in the world of Star
Trek Voyager? Talk about uneasy. Lieutenant Torres is 50 percent human and 50
percent Klingon. She's also 100 percent pregnant. Like any caring parent, she
doesn't want her unborn child to be teased for having a forehead that looks
like...well, like a tire-tread. But, here's the twist. She can do something
about it.

Mmm, she threw in some blond hair, too.

And is this the limit? Or could we go even further? If you can eventually
isolate all these things, can you then build a creature that has never existed
before? For example, I would like the eyesight of a hawk, and I'd like the
hearing of a dog. Otherwise, I'm quite content to be exactly as I am. So, could
I pluck the eyesight and the hearing and patch it in?

ERIC LANDER: Well, we don't know. We really don't know how that
engineering occurs and how we can improve on it. It would be very much like
getting a whole pile of parts to a Boeing 777 and a whole pile of parts to an
Airbus, and saying, "Well, I'm going to mix and match some of these so it will
have some of the properties. I make it a little fatter, but I also want to make
it a little shorter." And by the time you were done you'd think you'd made lots
of clever improvements, but the thing wouldn't get off the ground.

It's a very complex machine, and going in with a monkey wrench to change a
piece...the odds are most changes we would make today, almost all changes we'd
make today, would break the machine.

ROBERT KRULWICH: We may not be able to genetically
modify humans or Klingons yet, but we do do it to plants and animals
every day. Look at this stuff: tobacco plants with a gene from a firefly. And
they used that same insect gene to create glowing mice. So, it's theoretically
possible that we could create humans with other advantages that borrowed from
other creatures.

ERIC LANDER: That's right. But the humility of science right now, is to
appreciate how little we know about how you could even begin to go about that.
What is the difference between the twentieth century and twenty-first
century biology is it's now our job, in this century, to figure out how the
parts fit together.

ROBERT KRULWICH: And just as the twentieth century was
winding down, the race to finish the genome was reaching full throttle. The
competitive juices were flowing.

J. CRAIG VENTER: I am competitive, but when the social order doesn't
allow you to make progress, and it doesn't for most people, I say "To hell with
the social order. Well, I'll find a new way to do it."

TONY WHITE: It changed the paradigm on people, and people don't
like that. It was very offensive to these people: "How dare they," you know,
"rain on our parade? This is our turf."

ERIC LANDER: This was a challenge to the whole idea of public generation
of data. That's what offended people, was that we really felt deeply that these
were data that had to be available for everybody. And there was an attempt to
claim the public imagination for the proposition that these data were better
done in some private fashion and owned.

TONY WHITE: You know, you want to say, "Well, wait a minute. If you
could do it in two years, why weren't you doing it in two years? Why did we
have to come along to turn a 15 year project into a two year project."

ERIC LANDER: I must say the human genome project had a tremendous amount
of internal competition, even amongst the academic groups. There's competition
amongst academic scientists to be sure, and more than anything, there's
competition against disease. There's a strong sense that what we're trying to
find out is the most important information that you could possibly get.

TONY WHITE: I don't know. I mean, I hope that this will
all go away.

ROBERT KRULWICH: In June of 2000, it kind of did go
away. The contentious race to finish the genome came to an end. And the winner
was...?

Well, you probably heard. They decided to call it a tie.

FRANCIS COLLIINS: I think both Craig and I were really tired of the way
in which the representations had played out and wanted to see that sort of put
behind us. It was probably not good for Celera as a business to have this image
of being sort of always in contention with the public project. It
certainly wasn't good for the public project to be seen as battling with a
private sector enterprise.

ROBERT KRULWICH: President Clinton himself got the
public guys and the Celera guys to play nice, shake hands, and share the credit
for sequencing the genome.

TAPE OF PRESIDENT WILLIAM JEFFERSON CLINTON: "Nearly two centuries ago,
in this room, on this floor, Thomas Jefferson and a trusted aide spread out a
magnificent map. The aide was Meriwether Lewis, and the map was the product of
his courageous expedition across the American frontier all the way to the
Pacific. Today the world is joining us here in the East Room to behold a
map of even greater significance. We are here to celebrate the completion of
the first survey of the entire human genome. Without a doubt this is the most
important, most wondrous map ever produced by humankind."

ROBERT KRULWICH: And what does this map the President
is talking about...what does it look like? When we look across the landscape of
our DNA for the 30,000 genes that make up a human being, what do we
see?

ERIC LANDER: The genome is very lumpy.

ROBERT KRULWICH: Very lumpy?

ERIC LANDER: Very lumpy, very uneven. You might think, if we have 30,000
genes, they're kind of distributed uniformly across the chromosomes. Not so.
They're distributed like people are distributed in America: they're all bunched
up in some places, and then you have vast plains that don't have a lot of
people in them. It's like that with the genes. There are really gene-dense
regions that might have 15 times the density of genes, sort of New York City
over here. And there are other regions that might go for two million letters
and there's not a gene to be found in there. The remarkable thing about our
genome is how little gene there is in it. We have three billion letters of DNA,
but only one, one point five percent of it is gene.

ROBERT KRULWICH: One and a half percent?

ERIC LANDER: The rest of it, 99 percent of it, is stuff.

ROBERT KRULWICH: Stuff. This is a technical term?

ERIC LANDER: A technical term. More than half of your total DNA, is not
really yours. It consists of selfish DNA elements that somehow got into our
genomes about a billion and a half years ago, and have been hopping around,
making copies of themselves. To those selfish DNA elements...we're merely a
host for them. They view the human being just as a vehicle for transmitting
themselves.

ROBERT KRULWICH: Wait a second, wait a second, wait a
second. We have in each and every one of our cells that carry DNA, we have
these little, they're not beings, they're just hitchhiking? Hitchhikers?

ERIC LANDER: Hitchhiking chunks of DNA.

ROBERT KRULWICH: And they've been in us for how long?

ERIC LANDER: About a billion and a half years or so.

ROBERT KRULWICH: And all they've done is far as you can
say is stay there and multiply?

ERIC LANDER: Well, they move around.

ROBERT KRULWICH: And what is that? What do you call
that? I mean, it's not an animal, it's not a vegetable, it's just...

ERIC LANDER: It's just a gene that knows how to look out for
itself and nothing else.

ROBERT KRULWICH: And it's just riding around in us,
through time?

ERIC LANDER: It rides around in us. The majority of our genome is
this stuff, not us.

ROBERT KRULWICH: Wow. It is a little humbling to think
that we, the paragon of animals, the architects of great civilizations,
are used as taxicabs by a bunch of freeloading parasites who could care less
about us. But that's the mystery of it all.

ERIC LANDER: You come away from reading the genome recognizing that we
are so similar to every other living thing on this planet. And every innovation
in us—we didn't really invent it. These were all things inherited from our
ancestors.

This gives you a tremendous respect for life. It gives you respect for the
complexity of life, the innovation of life, and the tremendous connectivity
amongst all life on the planet.

ROBERT KRULWICH: We are, in a very real sense, ordinary
creatures. Our parts are interchangeable with all the other animals and even
the plants around us! And yet we know there is something about us that is
truly extraordinary.

What it is, we don't know. But what it does is it lets us ask questions,
and investigate and contemplate the messages buried in a molecule shaped like a
twisted staircase. That's what we, and maybe we alone can do.

Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation.

Sources

Links

National Human Genome Research Institutehttp://www.genome.gov/
The National Human Genome Research Institute is the hub of the Human Genome Project. Visit this site for accurate information about all aspects of the Human Genome Project and a wealth of carefully compiled resources, including a glossary of genetic terms and an extensive guide to other genome-related websites.

Glossary of Genetic Termshttp://www.genome.gov/glossary/index.cfm
Have you ever wished your dictionary could speak to you? This genome glossary offers a definition for almost any genetic term you can think of, provides a clear illustration of the term, invites you to explore related terms, and—ta da!—you can hear each term explained aloud by a specialist in the field of genetics.

Ensembl Browse a Genomehttp://useast.ensembl.org/index.html
There are thousands of websites related to genomics. This jump site regularly updates its annotated list of links and promises to help you sort through the genome Web jungle to find the best online resources.

GenomeWebhttp://www.genomeweb.com/
GenomeWeb is another useful jump site, which arranges its lists of links by category. If you are looking for information on a particular topic, say, a list of the top biogenetics research companies in the world, this site may be just what you need.

GeneCardshttp://www.genecards.org/
GeneCards, provided by the Weizmann Institute of Science, is a database of human genes and their relationship to diseases. It offers concise information about the functions of all the human genes we know about, and allows you to scroll through the code for each gene listed. This site is geared primarily towards scientists and researchers.

National Center for Biotechnology Informationhttp://www.ncbi.nlm.nih.gov/genome/guide/human/
This hub page for Human Genome Resources offers biomedical researchers around the world a one-stop resource for data that may be used in research efforts.

National Tay-Sachs and Allied Diseases Associationhttp://www.ntsad.org/
Visit this website for more information about Tay-Sachs, a devastating genetic disorder.

Cameron and Hayden Lord Foundationhttp://www.lordfoundation.org/
Cameron and Hayden Lord's stories are featured in "Cracking the Code of Life." Their parents began a foundation in their honor to provide resources for parents with terminally ill children, particularly those who suffer from Tay-Sachs. Peruse this thoughtful site for tips on caring for terminally ill children and to learn more about the disorder.

Cystic Fibrosis Foundationhttp://www.cff.org/
Find a clinical trial, volunteer your time, and learn about news and events on this comprehensive website about this debilitating genetic disorder.

American Cancer Societyhttp://www.cancer.org/
Learn about various types of cancer, find support and treatment, explore the latest research, and more on this extensive website.

Major funding for "Cracking the Code of Life" is provided by the National Science Foundation and the National Endowment for the Humanities, with additional funding for "Cracking the Code of Life" provided by the National Science Foundation.

National corporate funding for NOVA is provided by Cancer Treatment Centers of America.
Major funding for NOVA is provided by the David H. Koch Fund for Science, the Corporation for Public Broadcasting, and PBS viewers.